scholarly journals CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1091 ◽  
Author(s):  
Li Tian ◽  
Fan Cheng ◽  
Lei Wang ◽  
Wen Qin ◽  
Kun Zou ◽  
...  

Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl.

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4250
Author(s):  
Vera M. S. Isca ◽  
Joana Andrade ◽  
Ana Sofia Fernandes ◽  
Paulo Paixão ◽  
Clara Uriel ◽  
...  

The antimicrobial evaluation of twelve natural and hemisynthetic isopimarane diterpenes are reported. The compounds were evaluated against a panel of Gram-positive bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains and one vancomycin-resistant Enterococcus (VRE) strain. Only natural compounds 7,15-isopimaradien-19-ol (1) and 19-acetoxy-7,15-isopimaradien-3β-ol (6) showed promising results. Isopimarane (1) was the most active, showing MIC values between 6.76 µM against S. aureus (ATCC 43866) and 216.62 µM against E. faecalis (FFHB 427483) and E. flavescens (ATCC 49996). Compound (6) showed moderated activity against all tested microorganisms (MIC between value 22.54 and 45.07 µM). These compounds were found to be active against the methicillin-sensitive strains of S. aureus (CIP 106760 and FFHB 29593), showing MIC values of 13.55 (1) and 22.54 (6) µM. Both compounds were also active against vancomycin-resistant E. faecalis (ATCC 51299) (MIC values of 54.14 and 45.07 µM, respectively). In addition, the cytotoxicity of nine compounds 7,15-isopimaradien-3β,19-diol (2); mixture: 15-isopimarene-8β-isobutyryloxy-19-ol and 15-isopimarene-8β-butyryloxy-19-ol (3); 3β-acetoxy-7,15-isopimaradiene-19-ol (5); 19-acetoxy-7,15-isopimaradiene-3β-ol (6); 3β,19-diacetoxy-7,15-isopimaradiene (8); 15-isopimarene-8β,19-diol (9); 19-O-β-d-glucopyranoside-7,15-isopimaradiene (10); lagascatriol-16-O-β-d-glucopyranoside (11) and lagascatriol-16-O-α-d-mannopyranoside (12) was evaluated in the human breast cancer cell line MDA-MB-231. Isopimarane (2) was the only compound showing some cytotoxicity. The IC50 value of compound (2) was 15 µM, suggesting a mild antiproliferative activity against these breast cancer cells.


Author(s):  
Devi Nisa Hidayati ◽  
Fatimatuz Zahroh ◽  
Lina Wahyuni ◽  
Ibrahim Arifin

Ocimum basilicum L has proven to have in vitro cytotoxic activity against breast cancer cells. Pathways that cause cell death can involve one of the proteins, which is BCL-2. This study aims to determine the decrease of BCL-2 protein expressions in breast cancer cells (T47D and MCF-7) tat are treated with the ethanol extract of Ocimum basilicum L. Ocimum basilicum L. was extracted using the maceration method with 70% ethanol solvent. The concentration of ethanol extract of Ocimum basilicum L. used to see the expression of BCL-2 protein in T47D and MCF-7 cells was 199 µg/ml and 388 µg / mL. The observation of BCL-2 protein expression is using immunocytochemical methods of T47D and MCF-7 cancer cells. The results showed that the ethanol extract of Ocimum basilicum L could reduce BCL-2 protein expression in breast cancer cells (T47D and MCF-7) at concentrations of 199 µg/ml and 388 µg/ml, respectively.


2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


1998 ◽  
Vol 55 (6) ◽  
pp. 841-851 ◽  
Author(s):  
R.Jeffrey Baumann ◽  
Tammy L. Bush ◽  
Doreen E. Cross-Doersen ◽  
Elizabeth A. Cashman ◽  
Paul S. Wright ◽  
...  

2014 ◽  
Vol 32 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  
YUICHI KINOSHITA ◽  
KATSUHIKO YOSHIZAWA ◽  
KEI HAMAZAKI ◽  
YUKO EMOTO ◽  
TAKASHI YURI ◽  
...  

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